Pipeline update: 8 recent advancements in liver disease therapy

Many chronic liver complications such as autoimmune hepatitis and nonalcoholic fatty liver disease do not have approved therapies for direct treatment, but the current hepatology pipeline includes several candidates that have recently demonstrated safety in early trials and some that met top-line phase 3 results.

Healio Gastroenterology and Liver Disease presents the following reports on investigative therapies for autoimmune hepatitis, NAFLD, cholangiocarcinoma, hepatocellular carcinoma, and a rapid hepatitis B surface antigen test.

Lipocine fatty liver therapy leads to high rates of NAFLD resolution

LPCN 1144 significantly reduced liver fat in patients with nonalcoholic fatty liver disease after 16 weeks, according to a press release from the manufacturer, Lipocine.

“We are encouraged by the Liver Fat Study results, especially the extent of the observed NAFLD resolution which improved over eight-week interim results with potential for further improvement upon longer treatment,” Mahesh V. Patel, PhD, chairman, president and CEO of Lipocine, said in the release. “We look forward to conducting further clinical testing with LPCN 1144, in biopsy confirmed NASH subjects.” Read more

Givosiran reduces annual attacks, ALA levels in acute hepatic porphyria

Alnylam Pharmaceuticals announced that givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyria, met its ENVISION phase 3 primary efficacy endpoint of reduction in the annualized rate of composite porphyria attacks compared with placebo, according to a press release and conference call.

“Patients living with [acute hepatic porphyria (AHP)] experience debilitating and sometimes life-threatening neurovisceral attacks as well as chronic disease manifestations which negatively impact their quality of life,” Akshay Vaishnaw, MD, PhD, president of research and development at Alnylam, said in the release. “Based on these results, we believe givosiran has the potential, if approved, to be a transformative medicine for AHP patients and their families.” Read more

Stero Biotechs begins trial of CBD to reduce steroid use in autoimmune hepatitis

Stero Biotechs received Ethics Committee approval by Israel’s Ministry of Health to begin patient enrollment in a study of cannabidiol to reduce the dose and duration of steroid therapy in patients with liver disease, according to a press release.

The company will enroll 15 patients with autoimmune hepatitis in a phase 2 clinical trial of ST-AH-01 cannabidiol (CBD) formulation at the Rabin Medical Center in Israel. Read more

FDA grants orphan drug designation for cholangiocarcinoma therapy

Mundipharma EDO and Imbrium Therapeutics announced that the FDA granted orphan drug designation to etoposide toniribate for the treatment of cholangiocarcinoma, according to a press release.

“We are pleased that the FDA has recognized etoposide toniribate as a potential treatment for relapsed/refractory biliary tract cancer,” Thomas Mehrling, MD, PhD, CEO of Mundipharma EDO, said in the release. “As a company we are focused on developing treatments for rare and difficult-to-treat cancers and getting them to patients as rapidly as possible. We look forward to accelerating the development of etoposide toniribate, in conjunction with Imbrium Therapeutics, with a global phase 3 trial with sites in [the European Union], U.S., Australia and other countries.” Read more

Abbott receives CE Mark for rapid diagnostic HBV surface antigen test

Abbott received CE Mark for the company’s Determine HBsAg 2 test, a rapid diagnostic test designed to detect hepatitis B surface antigen, according to a press release.

“To achieve the WHO targets, 107 million HBV-infected people need to be urgently diagnosed, especially in highly endemic regions in Africa and Asia,” Damian Halloran, vice president of Infectious Disease-Emerging Markets at Abbott, said in the release. “The unparalleled sensitivity, portability and ease-of-use of the Determine HBsAg 2 provides life-changing technology that can dramatically scale up testing services so more infected people can know their status and get treatment earlier.” Read more

Phase 3 trial of pembrolizumab for advanced HCC fails to meet primary endpoints

The addition of pembrolizumab to best supportive care failed to extend survival among patients with advanced hepatocellular carcinoma who received prior systemic therapy, according to study results released by the agent’s manufacturer.

The randomized phase 3 KEYNOTE-240 trial included 413 patients with advanced HCC who received prior systemic therapy. Read more

Ocaliva shows fibrosis improvement in NASH

Intercept Pharmaceuticals announced that Ocaliva met its phase 3 study primary endpoint of fibrosis improvement by 1 stage or more with no worsening of nonalcoholic steatohepatitis, according to a press release and investor call.

“Fibrosis is currently the only NASH histology endpoint that predicts liver-related adverse clinical outcomes and all-cause mortality,” Mark Pruzanski, MD, president and CEO of Intercept, said during the investor call. “We believe today’s results represent a historic milestone in the development of novel treatments for patients with progressive fibrosis due to NASH, an indication for which there are no approved therapies.” Read more

Calliditas Therapeutics receives orphan drug designation for AIH, PBC

Calliditas Therapeutics announced that the FDA has granted the company two orphan drug designations, one for an autoimmune hepatitis therapy and one for a primary biliary cholangitis therapy, according to recent press releases.

“We are very pleased to receive ODD in the U.S. for the treatment of PBC,” Renée Aguiar-Lucander, CEO of Calliditas Therapeutics, said in a press release. “This confirms the high unmet medical need and further encourages us to continue to explore orphan indications in which we could leverage our existing expertise. This is a disease with few medical alternatives today, but with a lot of exciting research taking place.” Read more

Many chronic liver complications such as autoimmune hepatitis and nonalcoholic fatty liver disease do not have approved therapies for direct treatment, but the current hepatology pipeline includes several candidates that have recently demonstrated safety in early trials and some that met top-line phase 3 results.

Healio Gastroenterology and Liver Disease presents the following reports on investigative therapies for autoimmune hepatitis, NAFLD, cholangiocarcinoma, hepatocellular carcinoma, and a rapid hepatitis B surface antigen test.

Lipocine fatty liver therapy leads to high rates of NAFLD resolution

LPCN 1144 significantly reduced liver fat in patients with nonalcoholic fatty liver disease after 16 weeks, according to a press release from the manufacturer, Lipocine.

“We are encouraged by the Liver Fat Study results, especially the extent of the observed NAFLD resolution which improved over eight-week interim results with potential for further improvement upon longer treatment,” Mahesh V. Patel, PhD, chairman, president and CEO of Lipocine, said in the release. “We look forward to conducting further clinical testing with LPCN 1144, in biopsy confirmed NASH subjects.” Read more

Givosiran reduces annual attacks, ALA levels in acute hepatic porphyria

Alnylam Pharmaceuticals announced that givosiran, an investigational RNAi therapeutic in development for the treatment of acute hepatic porphyria, met its ENVISION phase 3 primary efficacy endpoint of reduction in the annualized rate of composite porphyria attacks compared with placebo, according to a press release and conference call.

“Patients living with [acute hepatic porphyria (AHP)] experience debilitating and sometimes life-threatening neurovisceral attacks as well as chronic disease manifestations which negatively impact their quality of life,” Akshay Vaishnaw, MD, PhD, president of research and development at Alnylam, said in the release. “Based on these results, we believe givosiran has the potential, if approved, to be a transformative medicine for AHP patients and their families.” Read more

Stero Biotechs begins trial of CBD to reduce steroid use in autoimmune hepatitis

Stero Biotechs received Ethics Committee approval by Israel’s Ministry of Health to begin patient enrollment in a study of cannabidiol to reduce the dose and duration of steroid therapy in patients with liver disease, according to a press release.

The company will enroll 15 patients with autoimmune hepatitis in a phase 2 clinical trial of ST-AH-01 cannabidiol (CBD) formulation at the Rabin Medical Center in Israel. Read more

FDA grants orphan drug designation for cholangiocarcinoma therapy

Mundipharma EDO and Imbrium Therapeutics announced that the FDA granted orphan drug designation to etoposide toniribate for the treatment of cholangiocarcinoma, according to a press release.

“We are pleased that the FDA has recognized etoposide toniribate as a potential treatment for relapsed/refractory biliary tract cancer,” Thomas Mehrling, MD, PhD, CEO of Mundipharma EDO, said in the release. “As a company we are focused on developing treatments for rare and difficult-to-treat cancers and getting them to patients as rapidly as possible. We look forward to accelerating the development of etoposide toniribate, in conjunction with Imbrium Therapeutics, with a global phase 3 trial with sites in [the European Union], U.S., Australia and other countries.” Read more

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Abbott receives CE Mark for rapid diagnostic HBV surface antigen test

Abbott received CE Mark for the company’s Determine HBsAg 2 test, a rapid diagnostic test designed to detect hepatitis B surface antigen, according to a press release.

“To achieve the WHO targets, 107 million HBV-infected people need to be urgently diagnosed, especially in highly endemic regions in Africa and Asia,” Damian Halloran, vice president of Infectious Disease-Emerging Markets at Abbott, said in the release. “The unparalleled sensitivity, portability and ease-of-use of the Determine HBsAg 2 provides life-changing technology that can dramatically scale up testing services so more infected people can know their status and get treatment earlier.” Read more

Phase 3 trial of pembrolizumab for advanced HCC fails to meet primary endpoints

The addition of pembrolizumab to best supportive care failed to extend survival among patients with advanced hepatocellular carcinoma who received prior systemic therapy, according to study results released by the agent’s manufacturer.

The randomized phase 3 KEYNOTE-240 trial included 413 patients with advanced HCC who received prior systemic therapy. Read more

Ocaliva shows fibrosis improvement in NASH

Intercept Pharmaceuticals announced that Ocaliva met its phase 3 study primary endpoint of fibrosis improvement by 1 stage or more with no worsening of nonalcoholic steatohepatitis, according to a press release and investor call.

“Fibrosis is currently the only NASH histology endpoint that predicts liver-related adverse clinical outcomes and all-cause mortality,” Mark Pruzanski, MD, president and CEO of Intercept, said during the investor call. “We believe today’s results represent a historic milestone in the development of novel treatments for patients with progressive fibrosis due to NASH, an indication for which there are no approved therapies.” Read more

Calliditas Therapeutics receives orphan drug designation for AIH, PBC

Calliditas Therapeutics announced that the FDA has granted the company two orphan drug designations, one for an autoimmune hepatitis therapy and one for a primary biliary cholangitis therapy, according to recent press releases.

“We are very pleased to receive ODD in the U.S. for the treatment of PBC,” Renée Aguiar-Lucander, CEO of Calliditas Therapeutics, said in a press release. “This confirms the high unmet medical need and further encourages us to continue to explore orphan indications in which we could leverage our existing expertise. This is a disease with few medical alternatives today, but with a lot of exciting research taking place.” Read more